Methyl iodide → 1-Acetyl-6-bromo-5-fluoro-2,2-dimethylindolin-3-one

HRID 331051Notes

Reaction equation

HRID 331051 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([F:14])=[C:10]([Br:13])[CH:11]=2)[C:6](=[O:15])[CH:5]1[CH3:16])(=[O:3])[CH3:2].[H-].[Na+].I[CH3:20]>C1COCC1>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([F:14])=[C:10]([Br:13])[CH:11]=2)[C:6](=[O:15])[C:5]1([CH3:20])[CH3:16])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 710896491-Acetyl-6-bromo-5-fluoro-2-methylindolin-3-one

Product 1

HCID 710896451-Acetyl-6-bromo-5-fluoro-2,2-dimethylindolin-3-oneYield 35.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of 1-acetyl-6-bromo-5-fluoro-2-methylindolin-3-one (D88) (800 mg, 2.80 mmol) in THF (20 mL) at 0° C. was added sodium hydride (224 mg, 5.59 mmol). After stirring for 10 min, iodomethane (0.210 mL, 3.36 mmol) was added to the mixture. The mixture was allowed to warm to RT. The mixture was stirred for 1 hour at RT. The reaction was quenched with addition with saturated NH4Cl aq. and the mixture was poured into water (100 mL). The mixture was extracted with ethyl acetate (30 mL×3). The organic layers were combined, washed with brine (100 mL), dried over MgSO4, filtered and evaporated in vacuo. The crude residue was purified by chromatography on silica, eluting with a gradient of 0-30% ethyl acetate in cyclohexane to give title compound (300 mg). LCMS (A): m/z (M+H)+ 300/302, C12H11BrFNO2 requires 299/301 (acidic).

Workup

  1. stirringThe mixture was stirred for 1 hour at RT
  2. customThe reaction was quenched with addition with saturated NH4Cl aq.
  3. additionthe mixture was poured into water (100 mL)
  4. extractionThe mixture was extracted with ethyl acetate (30 mL×3)
  5. washwashed with brine (100 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude residue was purified by chromatography on silica
  10. washeluting with a gradient of 0-30% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-321415bcbe764ada95c0b27921d1c3ec
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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